Hybridization histochemical localization of activin receptor subtypes in rat brain, pituitary, ovary, and testis.

Abstract

We have studied the distribution of activin receptor gene expression in the brain, pituitary, ovary, and testis of the adult rat by in situ hybridization, using probes complementary to the mRNAs encoding the mouse activin receptor subtypes II and IIB (ActRII and ActRIIB). Throughout the brain, ActRII mRNA expression was stronger than that of ActRIIB, and the patterns of expression were similar, although not identical. The most intense sites of activin receptor gene expression were the hippocampal formation, especially the dentate gyrus (ActRII), taenia tecta, and induseum griseum; the amygdala, particularly the amygdaloid-hippocampal transition zone; and throughout the cortical mantle, including the primary olfactory cortex (piriform cortex and olfactory tubercle); other regions of the cortex showing lesser degrees of hybridization included the cingulate cortex, claustrum, entorhinal cortex, and subiculum. In addition, moderate levels of expression were observed in several hypothalamic areas involved in neuroendocrine regulation, such as the suprachiasmatic, supraoptic, paraventricular, and arcuate nuclei. Moreover, activin receptors were also expressed in regions with inputs to the hypothalamus, both in the forebrain (bed nucleus of the stria terminalis and medial preoptic area) and within the brainstem (nucleus of the solitary tract, dorsal motor nucleus of the vagus, locus coeruleus, and mesencephalic raphé system). ActRII mRNA was observed in the intermediate lobe of the pituitary and, less prominently, in the anterior lobe, whereas ActRIIB appeared to be weakly expressed throughout all three pituitary divisions. In both male and female gonads, activin receptor message was clearly present in germ cells, and ActRII was the predominant form. In the ovary, in addition to an intense signal in the oocyte, activin receptor was expressed in corpus luteum and granulosa cells during diestrous day 1. In the testis, there was a strong ActRII signal in rounded spermatids, and a moderate signal in pachytene spermatocytes. In contrast, ActRIIB was absent within tubules, but weakly expressed in interstitial and Leydig cells. This is the first report of the distribution of activin receptor message in adult mammalian tissues. Although consistent with some previously suggested functional associations of activin-containing pathways in the brain, this pattern of expression suggests a greater role for activin than was previously appreciated in cortical, limbic, and somatosensory pathways and in the maturation of germ cells in the gonads of both male and female rats.

Expression and localization of activin receptors during endochondral bone development

“…The anti-ActRI antibody clearly recognized type I activin receptor after incubation with peptide Nglycosidase F (PNGase F) (10). Furthermore, these antibodies can be used for immunohistochemistry: gonads, brain and pancreatic islets, the tissues known to express activin and activin receptors, were stained positively by this method (6,10,12,13), and the immunodistributions of activin b A molecules in testis and ActRII molecules in brain were consistent with the expression of mRNA evaluated by in situ hybridization (10,12,14,15).…”

Activin A Signaling Induces Smad2, but Not Smad3, Requiring Protein Kinase A Activity in Granulosa Cells from the Avian Ovary

“…Thus, active TGF-␤-like ligands must exist within the follicle to drive nuclear accumulation of Smad2. Notably, granulosa cells actively secrete activin A, and they express cognate activin receptors (22,23,26), suggesting autocrine signaling in ovarian cells. Activin is therefore a possible candidate for an autocrine ligand that triggers activation and nuclear translocation of Smad2.…”

“…There is increasing evidence suggesting that activins are not only endocrine regulators of FSH availability but also potent effectors of autocrine or paracrine intraovarian signaling. Activin receptors and downstream Smad proteins are present in rat ovaries (22)(23)(24)(25)(26), and activins apparently play important roles in regulation of folliculogenesis and follicular function (27)(28)(29)(30). However, the knowledge about granulosa cells and how they respond to Smad signaling and its regulation is still rudimentary.…”

Human testicular germ cell tumours express inhibin subunits, activin receptors and follistatin mRNAs

“…The expression levels in the non-seminomas were significantly British Journal of Cancer (1997) 76(9) Kaipia et al, 1993;Cameron et al, 1994) and in the human teratocarcinoma cell line Tera-2 ( de Jong et al, 1993;RHN van Schaik, unpublished results). Our inability to detect ActRIIB expression in one non-seminoma, a mature teratoma, is in line with the down-regulation of ActRIIB mRNA levels when Tera-2 cells are differentiated by retinoic acid (de Jong et al, 1993).…”

“…Inhibin and activin are secreted by Sertoli cells ( de Jong, 1988;de Winter et al, 1993), while activin can also be produced by peritubular myoid cells (de Winter et al, 1994). Germ cells express activin receptors (Kaipia et al, 1991;de Winter et al, 1992;Cameron et al, 1994), bind activin and inhibin , and respond to inhibin and activin administration (van Dissel-Emiliani et al, 1989;Mather et al, 1990).…”